Clinical Effects and Antivenom Dosing in Brown Snake (Pseudonaja spp.) Envenoming — Australian Snakebite Project (ASP-14)

Abstract

BackgroundSnakebite is a global health issue and treatment with antivenom continues to be problematic. Brown snakes (genus Pseudonaja) are the most medically important group of Australian snakes and there is controversy over the dose of brown snake antivenom. We aimed to investigate the clinical and laboratory features of definite brown snake (Pseudonaja spp.) envenoming, and determine the dose of antivenom required.Methods and FindingThis was a prospective observational study of definite brown snake envenoming from the Australian Snakebite Project (ASP) based on snake identification or specific enzyme immunoassay for Pseudonaja venom. From January 2004 to January 2012 there were 149 definite brown snake bites [median age 42y (2–81y); 100 males]. Systemic envenoming occurred in 136 (88%) cases. All envenomed patients developed venom induced consumption coagulopathy (VICC), with complete VICC in 109 (80%) and partial VICC in 27 (20%). Systemic symptoms occurred in 61 (45%) and mild neurotoxicity in 2 (1%). Myotoxicity did not occur. Severe envenoming occurred in 51 patients (38%) and was characterised by collapse or hypotension (37), thrombotic microangiopathy (15), major haemorrhage (5), cardiac arrest (7) and death (6). The median peak venom concentration in 118 envenomed patients was 1.6 ng/mL (Range: 0.15–210 ng/mL). The median initial antivenom dose was 2 vials (Range: 1–40) in 128 patients receiving antivenom. There was no difference in INR recovery or clinical outcome between patients receiving one or more than one vial of antivenom. Free venom was not detected in 112/115 patients post-antivenom with only low concentrations (0.4 to 0.9 ng/ml) in three patients.ConclusionsEnvenoming by brown snakes causes VICC and over a third of patients had serious complications including major haemorrhage, collapse and microangiopathy. The results of this study support accumulating evidence that giving more than one vial of antivenom is unnecessary in brown snake envenoming.

Detection of venom after antivenom administration is largely due to bound venom

“…In studies of venom concentrations in Australian elapids venom is almost never detected post-antivenom (Isbister et al, 2013a;Allen et al, 2012). In this study we analysed three rare brown snake patients where there was venom detected postantivenom which was shown also to be mainly bound venom (Table 3).…”

“…Patients (>13 years of age) presenting with Russell's viper envenoming were included if venom was detected in the patients' serum with a Russell's viper venom specific ELISA, at least four serum samples at different time points were available for analysis and a pre-antivenom sample was available. Serial samples were also available from patients with brown snake envenoming who were recruited to the Australian snakebite project (Allen et al, 2012). All serum samples were immediately centrifuged after collection, then aliquoted and stored at À80 C until analysed.…”

“…All serum samples were immediately centrifuged after collection, then aliquoted and stored at À80 C until analysed. Ethics approval was obtained from Colombo University and the University of Peradeniya to cover hospitals in Sri Lanka and approval was obtained from several Human Research and Ethics Committees to cover all Australian hospitals involved (Allen et al, 2012).…”

“…ULaH was added to five samples from three patients with brown snake envenoming where venom had been detected post antivenom (Allen et al, 2012). These samples were assayed for venom and compared to samples where ULaH was not added.…”

Prothrombin activator-like toxin appears to mediate cardiovascular collapse following envenoming by Pseudonaja textilis

“…Indeed, death due to 'brown snakeinduced early cardiovascular collapse' is the most common cause of death from snake envenoming in Australia (Allen et al, 2012;Currie, 2004). The early cardiovascular collapse following the injection of snake venom has been shown in a number of in vivo studies (Chaisakul et al, 2012(Chaisakul et al, , 2013, but the toxins responsible for this effect are yet to be identified and the mechanism(s) behind cardiovascular collapse remain unclear.…”